To beat malaria and dengue, vaccinate the mosquitoes

If there’s one thing the malaria parasite wants, it’s to get inside the guts of a mosquito. Once there, it releases hundreds of wormlike cells that enter the human body through a bloodsucking bite. Now, scientists have found a way to make mosquitoes much less hospitable to this pathogen, as well as the one that causes dengue: stacking the insect’s gut with killer microbes that wipe out the invaders before they have a chance to cause disease.

Like humans and most other animals, mosquitoes are stuffed with microbes that live on and inside of them—their microbiome. When studying the microbes that make mosquitoes their home, researchers came across one called Chromobacterium sp. (Csp_P). They already knew that Csp_P’s close relatives were capable of producing powerful antibiotics, and they wondered if Csp_P might share the same talent.

The team cultured Csp_P in a sugar solution and in blood and fed both concoctions to mosquitoes whose natural microbiomes had already been eliminated with doses of antibiotics. As the scientists hoped, Csp_P quickly took over the mosquito’s gut after being ingested by means of the sugar solution—and even more quickly when it was fed to them in blood. In another experiment, done with mosquitoes that weren’t pretreated with antibiotics, Csp_P-fed mosquitoes were given blood containing the dengue virus and Plasmodium falciparum, a single-celled parasite that causes the most deadly type of malaria. Although a large number of the mosquitoes died within a few days of being infected by the Chromobacterium, the malaria and dengue pathogens were far less successful at infecting the mosquitoes that did survive, the team reports today in PLOS Pathogens. That’s good news: If the mosquito isn’t infected by the disease-causing germs, it is less likely to be able to transmit the pathogens to humans.

The team, from Johns Hopkins University in Baltimore, Maryland, also exposed the malaria parasite and dengue virus to lab cultures of Csp_P to test for anti-Plasmodium and antidengue activity. Here, too, they found that the bacteria inhibited the growth of the pathogens.

The researchers say there could be two mechanisms by which Csp_P fights off Plasmodium and dengue infections. First, because Csp_P is toxic to mosquitoes, it activates the insect’s immune system. This has the collateral benefit of staving off infection from Plasmodium and dengue virus, which otherwise would have thrived in the mosquito’s gut. But that’s not all, says George Dimopoulos, a parasitologist at Johns Hopkins who led the research team. Because the bacterium also snuffs out Plasmodium and the dengue virus in the laboratory, it means Csp_P is producing toxic compounds that are killing the pathogens directly.

Dimopoulos and his colleagues believe Csp_P could be used to “vaccinate” mosquitoes against the malaria and dengue pathogens, perhaps through the use of sugar-baited traps that are already used to spread insecticide through populations of the pest. This would have the twin effect of killing most mosquitoes while severely curbing the survivors’ ability to spread disease. This one-two punch is “a unique property” for any malaria-control agent, says David Fidock, a microbiologist at Columbia University, who was not involved in the study. “No current malaria-control agent does both.”

Csp_P could also play a more direct role in combating malaria and dengue in humans. Because the compounds it secretes kill pathogens in the lab, these toxins could be turned into drugs to treat malaria and dengue in people.

Tanjore Balganesh, a medicinal chemist who heads the Indian Open Source Drug Discovery program in Bangalore for neglected diseases such as malaria and tuberculosis, is skeptical, however. Because Csp_P is so toxic to Plasmodium, the dengue virus, and even the mosquito that carries them, there is a good chance it could be damaging to human cells, too, he says. That’s not a death blow for this line of inquiry, however. “It’s still early days [for this research],” he says, “but no drug discovery program is without problems.”